The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The anorectic effect of oleic acid was independent of leptin and was accompanied by a decrease in the hypothalamic expression of neuropeptide Y. The short-chain fatty acid octanoic acid failed to reproduce the metabolic effects of oleic acid, and ICV coadministration of inhibitors of ATP-sensitive K+ channels blunted the effect of oleic acid on glucose production. This is the first demonstration that fatty acids can signal nutrient availability to the CNS, which in turn limits further delivery of nutrients to the circulation.
Address correspondence and reprint requests to Dr. Luciano Rossetti, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. E-mail:.
Received for publication 3 October 2001 and accepted in revised form 26 November 2001. Posted on the World Wide Web at http://www.diabetes.org/diabetes_rapids on 20 December 2001.
aCSF, artificial cerebral spinal fluid; CNS, central nervous system; FFA, free fatty acid; GIR, glucose infusion rate; HBP, hydroxypropyl-β-cyclodextrin; ICV, intracerebroventricular; KATP, ATP-sensitive K+ channel; LC-CoA, long-chain fatty acyl CoA; NPY, neuropeptide Y.